Efficacy Of Coadministration Of Rosuvastatin And Ezetimibe In Patients After Percutaneous Coronary Intervention

Background:Percutaneous coronary intervention(PCI)can alleviate the symptoms of angina in patients with acute coronary syndrome(ACS),but factors causing atherosclerosis such as dyslipidemia still exist in patients.Therefore,lipid-regulating and plaque stabilization therapy is of vital importance for patients after PCI.The cholesterol treatment test(CTT)Meta-analysis showed that for every 1mmol/L reduction in low-density lipoprotein(LDLC),the risk of major cardiovascular events was reduced by 21%,the risk of major coronary events was reduced by 24%,and the risk of major stroke was reduced by 24%.So LDL-C plays a central role in the pathogenesis of atherosclerotic cardiovascular disease(ASCVD).Many guidelines recommend LDL-C as the primary intervention target.The 2018 AHA American cholesterol guidelines recommend high-intensity statins for people at high risk once again.PROVE-IT study showed early benefits of cardiovascular events in ACS patients after PCI using high-intensity statins.However,it is difficult for high-intensity statin to break through the 6% principle in reducing lipid,which will lead to an increase in adverse reactions and an increased risk of diabetes.Research published in 2015 on IMPROVE-IT showed that the moderate intensity statin in combination with ezeomab could significantly reduce LDL-C,resulting in clinical benefits.Due to differences in race,genetic background,genetic polymorphism,and drug metabolism,Chinese population has lower blood lipid baseline and stronger statin sensitivity,moderate intensity statin is sufficient to achieve the expected target value and good benefits.Therefore,the Chinese guidelines recommend moderate-intensity statin as a commonly used drug for Chinese patients with dyslipidemia.However,there is still the problem of sub-standard blood lipid.DYSIS-China showed that only 23.9% of the high-risk group met the standard.The purpose of this study is to further explore how to select the initial lipid-lowering strategy to make the blood lipids of ACS patients reach the standard quickly,effectively and safely after PCI.Methods: In this study,10 mg of rosuvastatin was selected as moderate intensity statin and 20 mg of rosuvastatin as high-intensity statin,to explore a rapid,effective and safe strategy for blood lipid reaching standard in ACS patients after PCI.Study was designed to be a prospective,single-center,open,randomized,controlled trial.From January to July in 2018,the acute coronary syndrome patients was diagnosed by Department of Cardiology,Xijing Hospital,treating successful PCI,whose residual stenosis of target lesion was less than 20% postoperative,TIMI blood flow was the third level.Those 104 cases accorded with the inclusion criteria as the research object was selected to divide to three groups.There were 35 cases in the 10 mg resuvastatin group,35 cases in the 20 mg resuvastatin group and 34 cases combined treatment group(10mg rosuvastatin + ezetimibe).All three groups received routine anticoagulation,antiplatelet and other basic treatments recommended by the guidelines,and were followed up for 6 months.Data collection included preoperative baseline data(age,gender,coronary heart disease risk factors,liver renal function,echocardiography,etc.),blood lipids(LDL-C,HDL-C,TC,TG)and endothelial microparticles(EMP),oxidized low density lipoprotein(Ox-LDL-C),intraoperative data related to the operation,postoperative other detail medication data,after 1 month,3 months,6 months,respectively follow-up blood lipids(LDL-C,HDL-C,TC,TG),liver and kidney function,drug adverse events,cardiovascular adverse events,and in 6 months,Ox-LDL-C and EMP was also followed up.The main endpoint of observation: LDL-C was up to standard(definition of standard: 1.Ldl-C<70mg/d L(1.8mmol/L);2.It is difficult to reduce the LDL-C baseline value to 70mg/d L,at least 50% of the original base value.3.The LDLC baseline value already be in the target value,and 30% of the original base value should be reduced.)Secondary observation endpoint: MACE events after PCI 6 months include myocardial infarctio,stroke,rehospitalization for unstable angina,coronary revascularization after 30 days and cardiovascular death.Other observational indicators: 1.Other blood lipid indexes: TC,TG,HDL-C,Non-HDL-C;2.The oxidation level of LDL-C: Ox-LDL-C and Ox-LDL-C were respectively compared with TC,LDL-C and HDL-C;3.Endothelial damaged indexe: endothelial microparticles.4.Adverse drug reactions: myalgia,fatigue,liver and kidney function damaged,creatine creatinase increased.Results: 1.The analysis of baseline data showed that the demographic data,basic vital signs,past medical history and auxiliary examination data of the patients in the three groups were comparable and balanced,and the number and location of target lesions and the number of stents were counted in the surgical data.There was no difference among the three groups.During the follow-up,drugs were used in each group,and the differences were not statistically significant.2.Intra-group comparison of serum lipid levels before and after treatment showed that TC,LDL-C and Non-HDL-C in the three groups were significantly lower after treatment than before treatment(all P<0.05),the 20 mg rosuvastatin group and the combination group effectively increased HDL-C(all P<0.05),but there was no statistical difference in 10 mg rosuvastatin with elevated HDL(P=0.078).3.The standard reaching rate of LDL-C in the 10 mg group of rosuvastatin at 1 month,3 months and 6 months after surgery was 46%(16/35),60%(21/35)and 60%(21/35),respectively.The 20 mg group of rosuvastatin was 54%(19/35),60%(21/35),and 63% (22/35),respectively.The combined group was 68%(23/34),79%(27/34)and 85%(29/34),respectively.There was no statistical difference between the three groups 1 month and 3 months after surgery,and there was a difference between the three groups at 6 months after surgery.However,there was no statistical difference in the lipid standard reaching rate between the 10 mg group and the 20 mg group at 6 months after surgery(2=0.06,P=0.500).The lipid standard reaching rate of the combined treatment group was significantly higher than that the 10 mg and 20 mg groups(?2=5.530,P=0.018;?2=4.503,P=0.031 respectively)4.At 1 month,3 months and 6 months after surgery,LDL-C was decreased by 9%,21% and 25% respectively in the 10 mg rosuvastatin group,11%,23% and 27% respectively in the 20 mg rosuvastatin group,and 18%,30% and 36% respectively in the combination group.At the first month follow-up,the LDL-C reduction in the combined group was higher than that in the other two groups(all P<0.05),the same trend was observed in the third and sixth month.Multivariate analysis of age,gender,current smoking,hypertension,diabetes and other risk factors was conducted by logistic binary regression.No significant factors were found to influence the change of LDL-C,so the compliance rate and decline rate of the combined treatment group were significantly higher than those of the other two groups.5.The decline of TC and non-HDL-C in the combined treatment group were higher than those in the other two groups(all P<0.05),there was no significant difference in TC and Non-HDL-C reduction between the 20 mg rosuvastatin group and the 10 mg rosuvastatin group(P>0.05).The trend of increasing HDL-C level in the 20 mg rosuvastatin group was greater than that in the 10 mg rosuvastatin group and the combination group,but the difference was not statistically significant(P>0.05).6.Six months after treatment,Ox-LDL-C,Ox-LDL-C/TC,Ox-LDL-C/ LDL-C,and OxLDL-C/HDL-C in the three groups were significantly lower than before treatment(all P<0.05),and the reduction of Ox-LDL-C and its ratio in the combined group was higher than that in the other two groups(all P<0.05),there was no significant difference in the reduction between the other two groups(all P>0.05).Ox-LDL-C level was independent of TC,HDL and LDL(all P>0.05).7.After 6 months of treatment,the number of endothelial particles in the three groups was significantly lower than that before treatment.However,there was no significant difference between the two groups(all P>0.05).8.There was no significant difference in the incidence of adverse reactions after 6 months of treatment among the three groups(?2=0.715,P=0.467).9.There was no significant difference in the incidence of MACE events among the three groups after 6 months of treatment(?2=1.128,P=0.661).Conclusions: 1.The amplitude and speed of LDL-C reduction in the combined treatment group was significantly higher than that in the 10 mg or 20 mg rosuvastatin group,with a high rate of reaching the standard.2.The reduction of TC,non-HDL-C?Ox-LDL-C and their ratio in the combined treatment group was significantly higher than that in the 10 mg or 20 mg rosuvastatin group.3.There was no statistically significant difference in the incidence of adverse drug reactions after PCI 6 months between the combined treatment group and the 10 mg or 20 mg rosuvastatin group,and the safety is good.4.There was no significant difference in the incidence of MACE events in ACS patients after PCI 6 months between the combined treatment and the 10 mg or 20 mg of resuvastatin.